Host-Versus-Graft (HVG) syndrome is a symptom complex that appears in parental-strain mice perinatally inoculated with F1 hybrid cells. Clinical pathologic and histopathologic studies have shown that parent F1 hybrid chimeras develop thrombocytopenia with fatal intestinal hemorrhage, renal disease resembling human systemic lupus erythematosus, serum abnormalities, liver disease, lymphoproliferative disorders and tumors. Recent immunopathologic studies have revealed an immunodeficiency state that seemed due to an inflammatory reaction that resulted in loss of thymic derived lymphocytes but spared bone marrow derived lymphocytes. The proposed work will explore the possibility that premature exposure of the lymphoreticular system to histocompatibility antigens may permanently impair the immune surveillance system and thus lead to later development of autoimmune diseases and tumors. A variety of in vivo and in vitro tests of immunocompetence in the early stages of HVG disease, coupled with sequential morphologic studies, will be used to study the etiology and pathogenesis of tumors in old parent/F1 chimeras. Search for viral agents will be initiated. Development of diagnostic and prognostic laboratory tests for experimental HVG disease may provide useful tests for clinical medicine as well.